AKA sinus node dysfunction.
- aminophylline is a complex of (theophylline and ethylenediamine)
| Asbestosis | Silicosis | Berylliosis |
|---|---|---|
| Primary from mining; Secondary exposure from using in manufacturing |
Sand blasting etc | Electronics manufacture |
| Fibrous form of Magneiusm Silicate | SiO2 crystals | ?Beryllium |
| Two Forms: Chrysolite - white asbestos, serpentien fibers - less harmful. Crosydolite - blue asbestos, straight fibers, more harmful |
||
| Pleural plaques 20 to 30 years after exposure - most on rib associated surfaace of pleura Benign effusions Diffuse pleural thickening Mesotheliomas Bronchial Carcinomas |
||
| SiO2 crystals persist cause necrosis of phagocytosing macrophages -> enzymes release -> lung damage. (cessation of exoposure doens't hald lung damage); Macrophage toxicity predisposes to post primary tuberculosis. |
||
| Lower lobe predilection | Upper lobe fibrosis with lymph nodes which can calcify | Upper lobe predilection. |
#2016GM-APR/Q01
RVH, Right sided Heart, RBB, Posterior MI
[!INFO] Summary
LBBB RBBB Always pathological Can be benign Causes LAD No effect on axis Affects MI diagnosis No effect on MI diagnosis
[!TIP] Mnemonic: It seems that increase in ventricular afterload can cause ipsilateral bundle branch blocks.
? cause of LAD in LBBB?
?is it because The counterbalancing effect of RV depolarization on the axis is lost as the RV depolarizes later??
Verapamil is a suitable alternative for adenosine if it it contraindicated.
[!INFO] AV nodal blocking drugs
Source: Harrison's
Mnemonic: AV nodal Blocking drugs : AVB -> Adenosine, verapamil, beta blockers (after trying vagal maneuvers)
(+? others)
[!INFO] Mnemonics:
Adenocarcinoma : Acchis
SQCs : Smokers
4. Diagnosis: By anti-P/Q-type voltage-gated calcium channel (VGCC) antibody testing and high frequency RNS (repetitive nerves stimulation)
5. Targeted therapy for symptomatic LEMS with 3,4-diaminopyridine is usually first line.
6. Refractory cases : immunosuppressants and plasma exchange.
[!TIP] Hypercalcemia: Abdominal groans, psychich moans and renal stones.
Allergic bronchopulmonary aspergillosis
[[passMedicine Summaries#Hypersensitivity pneumonitis (HP)|Hypersensitivity Pneumonitis]]
| Features | ABPA |
EGPA (Churg strauss) |
Hypersensitivity Pneumonitis |
|---|---|---|---|
| Presentation | Presents as poorly controlled asthma | Can present with Difficult to control asthma | |
| Clinical pearls | Can be unmasked with monteleukast | ||
| Blood and serology | Eosinophilia, IgE levels always positive. Skin prick test for aspegillus is +ve. |
Eosinophilia + pANCA +ve |
No eosinophilia CD8+ predominant BAL aspirate |
| CXR | Xray changes – migratory but persistent infiltrates. Proximal bronchiectasis, Upper lobe fibrosis if recurrent, | Flitting pulmonary infiltrates | CXR – non specific CT – centrilobular nodules. |
| Clinical features | Fever, wheeze, cough | Vasculitic features: mononeuritis multiplex, Rapidly proliferating glomerulonephritis, Tender subcutaneous nodules | Acute: Fever, cough, No wheezing Chronic: SOB, fatigue, dyspnoea Crackles |
| Treatment | Steroids + itraconazole + voriconazole | Responds well to steroids | Steroids + allergen avoidance |
- 3 times more common in women
- most commonly diagnosed in people aged 20-40 years
- Relapses are caused by acute inflammation causing myelin damage and conduction block.
- Demyelination has a prediliction of cervical spinal cord, optic nerves, corpus callosum, cerebellar connections of the brainstem. (contrast with [[HIV-AIDS#^13ac5c|PML]] where spinal cord and optic nerves are spared)
- PML can be cause by reactivation of JC virus which in turn can be promoted by therapy with natalizumab!!. (which is used to treat MS)
| Metformin | Biguanide | Insulin sensitiztion Reduce hepatic gluconeogenesis.It activates AMPK (AMP activated protein kinase) | GI side effects Lactic acidosis (risk in renal/liver/heart failure – contrindications) No weight gain May reduce apetite, STOP when eGFR < 30 | Reduced GI B12 absorption The usual first line agent, can be combined with other | Lower FBS by about 50 mg/dL Lowers HbA1C by about 1% |
Mechanism of action: Increases intracellular c-AMP potentiated insulin secretion.
After initial detection on the FBC, the investigation of choice is immunophenotyping by flow cytometry to reveal cell surface markers typical of CLL, including CD5, CD19 and CD20.
Source-YouTube
Source-YouTube
Source-YouTube
| MHC I | MHC II |
|---|---|
| Present on ALL nucleated cells | Presenton APCs |
| Binds CD8 receptor | Binds CD4 receptors |
| Stimultes Cytotoxic T cells | Stimulates T helper cells |
GVHD can occur after allogenic haemotopoietic cell transplantation or with solid organs containing lymphoid tissue. (Bowel transplant was one example)
GVHD arises when immune cells transplanted from a non-identical donor graft into the recipient (host), recognize the host cells as "foreign," thereby initiating a graft-versus-host reaction.
- **Dermatitis** - painful, pruritic rash. (not vessicles like in the mnemonic)
- 
#2016GM-OCT/Q29
Leishmaniasis has a wide spectrum of disease
At one end of the spectrum, mucosal leishmaniasis (ML) and leishmaniasis recidivans (LR) are caused by oligoparasitic disease associated with a marked cellular immune response.
The center of the spectrum consists of localized cutaneous leishmaniasis (LCL), which is the most common clinical presentation.
At the opposite end of the spectrum, diffuse cutaneous leishmaniasis (DCL) is caused by polyparasitic disease with a predominance of parasitized macrophages and no granulomatous inflammation.
This is the commoner form in Sri Lanka.
Symptoms:
"black fever" refers to the grayish skin colouration that develop probably due to cytokine dysregulation.
Main reservoir in Asia is dogs and foxes. (mnemonic: Dogs itch)
#hepatosplenomegaly with #lymphadenopathy (but lymphadenopathy isn't common)
Commonest presentation is with abrupt onset fever with chills and rigors which then continues for weeks.
Splenomegaly seen by second week followed by hepatomegaly.
Lymphadenopathy is seem but is rare in the indian subcontinent.
weight loss
Pancytopaenia can lead to thrombocytopenia which causes epistaxis, petechiae, purpura or other bleeding.
Complications: DIC or macrophage activation syndrome.
Diagnosis: Identification of the organisms in aspirate of bone marrow or liver or spleen.
Other investigations:
Treatment: pentavalent antimony salts (Sodium stibogluconate / melumine antimoniate) OR IV liposomal amphotericin B and IM paromomycin. Some patients develop post kalar-azar dermal leishmaniasis.
Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL); it is characterised by a macular, maculopapular, and nodular rash in a patient who has recovered from VL and who is otherwise well.
[!INFO] What "Effacement" means:
"Errasing, dissapearance". (like effacement of the cervix)In this phenomenon, the normal interdigitated foot processes are finally reorganized into a broad flattened process like a paddle. The morphological process of the foot process effacement has not fully elucidated. Source
FSGS is more likely with inflammatory conditions like SLE - PasTest
| Primary FSGS | Secondary FSGS |
|---|---|
| Sometimes responds to steroids, failure of steroids is common. Other immunosuppresants are used. | Usually poor response to steroids. ACEi are better |
| Presents as massive proteinuria, haematuria and hypertension. | Can be caused by any process which reduces functioning number of nephrons (eg. nephrectomy) |
| (nephrectomy, hypertension, gross obesity, IgA nephropathy, HIV, CMV, EBV) |
in embryonic mice, parietal epithelial cells can migrate to the visceral layer and replace damaged podocytes (Right) but in the older mice, such replacement can't occur and results in sclerosis. (left)
[!TIP]
MCD and FSGS are like cousins; FSGS is the evil cousin.
c | Electron microscopy image showing subepithelial electron-dense deposits (spikes)(black arrows) and basement membrane material between the electron-dense deposits (white arrows; 4,800×).
[!INFO] Stroke guidelines
[[NG-Management-of-Stroke-Book.pdf]]
And along with the above, high intensity statin should be commenced immediately.
#2016GM-OCT/Q25
#2016GM-APR/Q06
| Leads with ST segment elevations | Affected myocardial area | Occluded coronary artery (cuprit) |
|---|---|---|
| V1–V2 | Septal | Proximal LAD. |
| V3–V4 | Anterior | LAD. |
| V5–V6 | Distal LAD, LCx or RCA. | |
| I, aVL | Lateral | LCx. |
| II, aVF, III | Inferior | 90% RCA. 10% LCx. |
Suspect and look for right ventricular infarction in all patients with inferior STEMI
Suspect when:
ST elevation in V1
ST elevation in V1 and ST depression in V2 (highly specific for RV infarction)
Isoelectric ST segment in V1 with marked ST depression in V2
ST elevation in III > II (Lead III is more rightward facing than lead II and hence more sensitive to the injury current produced by the right ventricle)
The "posterior wall" may not even exist. Source but it does for exam purposes.
- Isolated posterior wall STEMI is uncommon.
- Tall R waves in V1 and V2 are reciprocals of Q waves in the posterior wall.
| Killip class | Features | 30 day mortality |
|---|---|---|
| I | No clinical signs heart failure | 6% |
| II | Lung crackles, S3 | 17% |
| III | Frank pulmonary oedema | 38% |
| IV | Cardiogenic shock | 81% |
BCD + PRSTUvW
Bacterial overgrowh, Coeliac disease, Dermatitis herpetiformis
Parasites, Resection, Sprue, Tropical Srpue, Uv = radiation, Whipples
[!INFO] It takes 1 hour to process 1 unit
| type 1 PCKD | Type 2 PCKD |
|---|---|
| 85% of cases | 15% of cases |
| Presents earlier with renal failure |
[!TIP] Mnemonic: Don't confuse with PSC - PBC has 'cirrhosis' in the name -> liver tissue is inolved -> interlobular bile ducts are involved.
#2016GM-OCT/Q30
enterohaemorrhagic (EHEC) (aka STEC - shiga toxin producing E coli)But there are actually 5 types.
- ETEC causes watery diarrhea in resource-limited settings and is commonly found in food and water in areas without adequate sanitation
- EPEC (enteropathogenic) was the first E. coli pathotype identified as a causative agent of watery diarrhea primarily in infants and young children in resource-limited settings
- EAEC (enteroaggregative) is a causative organism of acute and chronic watery diarrhea in resource-limited and resource-rich regions
- EHEC/STEC produces Shiga-toxin and includes serotypes O157:H7, as well as others
- EIEC-induced diarrheal illness is uncommon due
Necator americanus ("American murderer")
and ancylostoma ceylonicum
#2022BSQ-OCT/Q5
| cyst | Scolex |
|---|---|
[!TIP] Mnemonic :"Solium polium" - solium = pork tapeworm.
Only pork tape worm causes cysticercosis
Taeniasis - tape worm in the intestine.
- Humans eat pig meat
- Pigs eat human poop.
- If humans eat human poop (own poop (autonifection) or someone else poop)-> neurocysticercosis
ONLY TAENIA SOLIUM causes CYSTICERCOSIS.
Probably the most common parasitic infection of the CNS.
Pigs -> intermediate host,
Humans -> definitive host.
cysticercosis results from humans acting as 🔖accidental intermediate hosts for the parasite
[!INFO] Humans are the only definitive hosts for Taenia saginata, solium and asiatica.
[!INFO] Humans eat pig meat -> taeniasis, Humans eat pig poop -> cysticercosis
Ingesting uncooked pork -> ingestion of cysts in pig muscle -> intestinal tape worm infection in the human.
Ingesting eggs in faeces from infected human -> cysticercosis -> possible neurocysticercosis.
In cysticercosis, eggs hatch into larva which migrate through the host body into various tissues.
[!INFO] Phases of neurocysticercosis :
There are two forms; parenchymal (>60%) and extraparenchymal.
- Phase 1: viable phase -> parasite is implanting in tissue; no significant inflammation. Cyst may secrete immunosuppresive chemicals. Can last years or be very short.
- phase 2: early inflammatory stage: When ability to evade host response is lost. Inflammation begins. But parasite remains viable.
- Phase 3: host response begins eradicating parasite. Cyst degenerates.
- phase 4: non viable phase -> calcified granuloma formation.
A good detailed Source
[!TIP] overall summary
Granuloma formation is a histologic pattern of chronic inflammation.
Macrophages and tissue macrophages (histiocytes) usually form granulomas in order to eliminate an antigen which cannot be removed by a single macrophage.
- However, sometimes, granulomas are formed in the absense of an antigen, due to autoimmune diseases.
When a macrophage encounters something it cannot phagocytose, it secretes mediators (?cytokines) which promote migration of other macrophages to the site.
When many macrophages arrive at the site, they collectively undergo changes which allow them to form functional granulomas:
- Epithelialization : where the cell membranes begin to interdigitate.
- Giant cell formation.
- This is when multiple macrophages fuse to form a giant cell with multiple nuclei.
In addition, other types of immune cells are also recruited.The type of immune cell that is recruited and the cytokines secreted by it will determine how the granuloma 'matures'.
Specially, Th cells have a significant role to play here.
When some granulomas mature, the central macrophages undergo necrosis ->
- This is called a necrotizing granuloma and is charachteristic of certain diseases.
Other granulomas will undergo fibrosis. Also characteristic of some diseases.
The main patterns that we are concerned with are caseous vs non caseous necrosis and necrotizing vs. non nectrotizing granulomas.
[!INFO] Exerpt from the summary of the article above:
- Granuloma macrophages can undergo different types of specialized differentiation.
- Multiple additional types of cells can be recruited in the granuloma and influence its structure and function.
- Granulomas can form in response to large and small particles, which can be infectious agents or nonliving objects.
- Many granulomas occur in the context of inflammatory and autoimmune diseases in the absence of a known antigenic trigger.
Granuloma formation is a histologic pattern of chronic inflammation.
The particular pattern can suggestive of a particular disease
The pattern of inflammation can be classified in many ways. (necrotizing or not / Suppurative or not etc.)
This corresponds to the features of the granuloma after 'maturation'.
The prototypes are
monocytes in blood -> become macrophages in tissue (aka histiocytes)
histiocyte = tissue macrophage
| Disease | Pattern |
|---|---|
| Tuberculosis | Caseating (i.e absolutely no cellular structure) granuloma with occasional Langhans giant cells |
| Leprosy | Non caseating granuloma |
| Sarcoidosis | Non caseating, abundant activated macrophages |
| Cat Scratch disease | Rounded or stellate, central debris present. |
| Syphillitic gumma | Central necrosis but with preserved cell outlines, plasma cell infiltrate |
| GPA (granulomatosis with polyangitis) | presence of multinucleated giant cells, interstitial collagen alteration, and the presence of a polymorphous inflammatory infiltrate |
| Crohn's disease | Occasional non caseating granulomas with dense fibrous infiltrate |
[!INFO] Granuloma formation: Overview
Granulomas are formed when individual macrophages can't eliminate an antigen.
Then antigen presenting cells in the tissue recruit more macrophages from the circulation into the tissue.
Macrophages all clump around the antigen forming a granuloma.
The macrophages undergo a process called epithelialization where they take on the appearance of epithelial cells.
Their membranes begin to interdigitate and the nuclei swell.
Some of the macrophages will fuse to form Langhans giant cells.
The structure of the granuloma differs based on the triggering antigen.
In Tuberculosis, interferon gamma is a mediator of granuloma formation.
Other mediators like TNF-alpha are important in the formation of granulomas.
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that presents with rapidly developing, painful skin ulcers hallmarked by undermined borders and peripheral erythema. Epidemiological studies indicate that the average age of PG onset is in the mid-40s. Source
Pathergy is a feature.
[!INFO] Pathergy:
Pathergy is an exaggerated skin injury occurring after minor trauma such as bump, bruise, needle stick injury. A more severe injury, such as a surgical procedure, can result in persistent ulceration in a patient with pathergy. It typically occurs in patients with Behcet disease.
Pathergy occurs in :
- Sweet syndrome
- Behcet-disease
- Pyoderma ganrenosum
DD for neutrophillic dermatosi: Sweet syndrome
Biopsy: INTENSE neutrophilic infiltrate with no evidence of infection or vasculitis.
#2017GM-APR/Q10
Associated diseases are
Treatment: steroids and immunosuppresants.
aka acute febrile neutrophilic dermatosis.
#2022BSQ-OCT/Q2
Routes of malignant spread
Primary brain tumours are either
#2022BSQ-MAY Q27
Source:Medscape
Follicular cells : Papillary, follicular and anaplastic CA.
Parafollicular C cells : Medullary CA. (C cells are neuroendocrine cells and they produce [[Hormone Physiology#Calcitonin|Calcitonin]]).
[!INFO] Hot nodules are almost always noncancerous
However, the majority of thyroid nodules scanned are (Approximately 95 percent) are cold.
Most cold nodules are due to benign processes (>90%)
Cold nodules have an approximately 5% risk of being cancerous.
However, HOT nodules are almost never cancerous.
Both papillary and follicular CA are 3 times commoner in women.
Follicular develops at an older age.
Thyroglobulin is produced by differentiated thyroid CA. It can be used as a marker of recurrent after total thyroid ablation.
Are also usually cold nodules on radioiodine scan.
Commoner in iodine deficient areas.
Histology: encapsulated.
Follicular cells have a solid, trabercular or follicular growth pattern.
No characteristic nuclear features.
Differentiated from benign adenomas by
They arise from the follicular cells of the thyroid. The neoplastic cells are TSH sensitive as well, taking up iodine and producing thyroglobulin—a feature that is exploited diagnostically and therapeutically
Follicular carcinomas have less tendency for local metz (nodes) but higher risk of distant mets.
Distant mets for both types occur to lung and bone.
Hürthle cell carcinoma is a rare, more agrressive variant of follicular carcinoma. 5 year survival is 50 - 60%.
Makes up 2-3% of all thyroid malignancies.
Composed of distinct looking polygonal cells with acidophillic cytoplasm.
Associated with RAS mutation and RET/PTC oncogene.
[!INFO] Hurthle cells are seen in non malignant conditions as well
Hurthle cells are clasically seen in
- Hashimoto thyroiditis
- multinodular hypoplasia
- lymphocytic thyroidis
- Source
2-3% of thyroid CA.
They are associated with familial MTC (FMTC) syndromes.
So much so that there is a clinical distinction between identification of patient familial MTC and diagnosis a new sporadic MTC.
Parafollicular C cells produce calcitonin -> elevated calcitonin is diagnostic of MTC.
Inheritance of all familial forms of MTC and MEN2 are #autosomalDominant .
RET proto-oncogene mutations are seen in all MTC syndromes.
Approximately 80% of individuals with a RET genetic variant will develop medullary thyroid cancer at some point in their lives.
FTMC is a subtype of MEN2. FMTC patients have less probability of the other cancers of MEN2 but higher probability of medullary thyroid CA.
Familial cases are multifocal and bilateral.
Sporadic cases are unifolcal.
Histology:
Treatment:
Lymph node metastasis is common.
Total thyroidectomy with lymph node clearance is done.
Prophylactic thyroidectomy is done in children diganosed with MEN2 syndromes.
MEN2 is divided into three subtypes: type 2A, type 2B and Familial Medullary thyroid carcinoma (FMTC).
In treatment of MEN, to avoid intra op hypertension, resection of pheochromocytoma should be done before MTC resection.
[!TIP] Mnemonic for MEN syndromes
පා පා පි
පා මේ ෆි
මා මේ ෆි
[!WARNING] A very, very bad cancer!
It is rare but has the worst prognosis of all thyroid CAs.
Occurs in older adults (60-70) -> older adult with a thyroid nodule could have a dangerous thyroid CA.
1 year survival is a dismal 20%. Median survival is 5-6 months.
Anaplastic CA grows rapidly. Many patients present with local invasion (unresectable tumours) or cervial lymph node metastasis.
On histology, the tumour retains feature so epithelial cells (presence of desmosomes) but there are large areas of necrosis and bleeding. There is high mitotic activity.
In adults, bone mets are far more common than primary bone tumours.
Bone is the 3rd commonest site of metastatis next to Lung and liver.
Prostate and breast cancer (BC) are responsible for the majority of the skeletal metastases (up to 70%).
Other sources of bone mets : thyroid, renal cell carcinoma, lung cancer, melanoma
Bone mets are commonest in spine, pelvis and thigh.
Osteolytic :
Osteoblastic:
Mnenomic for sclerotic bone lesion:
#2023BSQ-NOV/Q12
Regarding prostate CA:
Pathologic fractures do occur, although they are generally less frequent than in cancers with predominantly osteolytic disease
Source
Multiple myeloma – The classic bone lesions in multiple myeloma are purely osteolytic due to increased bone destruction and suppressed bone formation.
Prostate cancer – Males with bone metastases from prostate cancer predominantly have osteoblastic (aka sclerotic) lesions with increased numbers of irregular bone trabeculae. Simultaneously, osteoclastic action is also increased.
Breast cancer - The great majority of breast CA produces osteolytic bone lesions, osteoblastic areas are also usually present
Renal cancer also commonly spreads to bone.
#2022BSQ-OCT/Q08
Plaques are raised lesions in the blood vessel.
Filled with cholesterol and cholesterol esters.
#2020BSQ-JUL/Q32
[!INFO] Response to vessel injury
Vessel injury of any cause produces the same stereotyped response. Intimal thickening is a stereotypical response to vessel injury.
Mechanism: Intimal injury stimulates migration of smooth muscle cells from the media OR from circulating precursors!. They arrive in the intima, undergo mitosis and produces extracellular matrix, forming a 'neointima'. This is analogous to scar formation elsewhere. Neointimal smooth muscle cells are non contractile but can undergo mitosis and greater synthetic capacity. This altered activation of neointimal smooth muscle cells is driven by cytokines produced by platelets, macrophages, endothelial cells and circulating complement and coagulation factors. Cytokines involved are PDGF, FGF, TGF-alpha (Platelet derived growth factors, Fibroblast growth factors, TGF-alpha).
Removal of the harmful stimulus will revert the phenotype of neotintimal muscle cells to their non proliferative (medial smooth muscle is non proliferative) state but the thickening they have produced is irreversible.
Intimal thickening is also a normal part of aging but because of outward remodeling, does not narrow vessels.
Risk factors for atherosclerosis have roughly multiplicative effects. 2 factors -X2 risk, 3 factors X7 risk.
Risk factors:
Dietary:
High intake of saturated fats raises lipid levels.
Trans unsaturated fats found in margarine are bad.
Omega 3 fatty acids in fish are good.
Exercise and moderate consumption of ethanol raises HDL levels.
CRP produced by 'cells in the plaque' increase adhesiveness of endothelial cells and CRP independently and strongly correlated with risk of infarction.
Lipoprotein a increases risk.
"The internal elastic lamina is a fenestrated sheet that forms the boundary between the intimal and medial layers, influencing both its mechanical and mass transport properties"
Neovascularization produces vessels which can rupture into the plaque and cause haemorrhage into it.
Atherosclerosis requires two factors
Anything that exacerbates these two factors will promote atherogenesis.
In the presence of lipids within the intima, macrophages become activated. When they 📑engulf lipids, they become foam cells.
Cytokines secreted by macrophages stimulate altered function and growth of smooth muscle cells of the media.
📑Smooth muscle cells proliferate and take on fibroblastic roles.
Smooth muscles + collagen produced by them form the fibrous cap of the plaque.
Plaques can
Factors which make a plaque unstable:
[!INFO] The response to injury hypothesis of atherosclerosis
- Views atherosclerosis as a chronic inflammatory process.
- There is interaction of lipoproteins, macrophages, T lymphocytes to cause progression of the lesion
- Main components of atherosclerosis:
- Endothelial injury with ⬆ adhesiveness and ⬆ permeability - the main component. Atherosclerosis begins at intact but dysfunctional endothelium.
- Endothelial dysfunction is promoted mainly by altered haemodynamics and hypercholesterolemia.
- Haemodynamics: Turbulence; as occurs at ostia, branch points and posterior wall of the aorta. Laminar flow is protective via gene induction.
- Hypercholesterolaemia - 1) directly causes endothelial dysfunction, 2)Promotes inflammation by formation of oxidised LDL and cholesterol crystals
- Dysfunctional endothelium promotes adhesion of inflmmatory cells including macrophages (which engulf LDL to become foam cells) and T lymphocytes (which set up chronic inflammation).
- Platelet adhesion
- Monocyte / macrophage adhesion and adtivation
- lipid and lipoprotein accumulation
- Smooth muscle cell recruitment by mediators produced by platelets, macrophages
- Smooth muscle cell proliferation.
Morphology:
The majority of plaque ruptures occurs in the proximal and middle of coronary arteries and distal ruptures are rare.
Source
#2022BSQ Q24
Secretin and CCK are endocrine hormones.
Secretin - role is to neutralize stomach effluent
Secretin stimulation test: Although secreting physiologically inhibits gastrin secretion, in the presence of a gastrinoma, secretin paradoxically increases gastrin secretion. This is the basis of the secretin stimulation test for gastrinoma.
#2022BSQ-OCT/Q24
See table 32.4 K and C.
Secretin glucagon family
Vasoactive intestinal peptide (VIP) -> Secreted by enteric NERVES -> Neurotransmitter, Stimulates insulin release, splanchnic vasodildation and intestinal secretion of water and electrolytes; also relaxes smooth muscles, including the lower esophageal sphincter and colon
Mnemonic: VIP readies the stomach and gut receival of food.
Glucose dependent insulinotropic polypeptide - GIP - - From duodenum, gastric antrum and ileum - stimulated by intraduodenal glucose -> incretin effect. (produced by K cells)
GLP-1 - The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, to limit postprandial glucose rise. Secreted by L cells in the ileum and colon.
Humans have almost no L cells proximal to the ligament of treitz (i.e in the duodenum) Source
Secretion is likely triggered by glucose in the duodenum as well as the rest of the gut as well. Source
Source
Only a small percentage of the produced GLP-1 reaches the liver and systemic circulation because of the action of DPP-IV.
[!TIP] Mnemonic: All of these hormones generally cause changes which promote digestion and absorption except for somatostatin
Somatostatin: somatostatin decreases endocrine and exocrine secretion and blood flow, reduces gastrointestinal motility and gallbladder contraction, and inhibits secretion of most gastrointestinal hormones.
Secretin: physiologic role increases pancreatic bicarbonate secretion and inhibits gastrin production. But in gastric CA, administration of secretin causes increased gastrin production. (paradoxically)
[!INFO] Elevated urobilinogen levels
#2020BSQ-NOV/Q04
Urobilinogen levels rise with increasing bilirubin production.
"Elevated urobilinogen levels may also be seen when the liver simply cannot remove urobilinogen from the portal venous blood, as occurs in severe liver disease, such as cirrhosis." - Source
[!INFO] Significance of active conjugated bilirubin secretion from hepatocytes
The active secretion of cojugated bilirugin into bile cannaliculi is rate limiting. But uptake of unconjugated bilirubin is very efficient.
Therefore, hepatocytes near the supplying veins will take up all the unconjugated bilirubin but may not be able to excrete all of it into the bile. Therefore, they reexcrete it into the sinusoids so that down stream hepatocytes can reuptake this conjugated bilirubin and help to excrete it into the bile canalliculi.
I.e more hepatocytes are recruited for excretion.
The transport proteins requried for reabsorption are affected in Rotor syndrome -> leads to conjugated and unconjugated hyperbilirubinaemia.(mostly conjugated)
[!TIP]
Note how all the intrahepatic causes of jaundice cause conjugated hyperbilirubinaemia.
?? are the only causes of unconjugated hyperbiliribunaemia CN , Gilbert and haemolytic anaemias?
[!INFO] DDx of conjugated hyperbilirubinaemia
And this table which Medscape made incredibly hard to copy.
From Harrisons
#2019BSQ-OCT/Q54
The complement system consists of a set of plasma glycoproteins.Source.
What follows are several images of how the complement system works;
Source
[!INFO] Functions of complement
- Promote inflammation through C3a, C4a and C5a
- Recruit cells (through chemoatractants)
- Kill targeted cells (bacteria)
- Solubilitze antigen-antibody complexes and remove them from circulation
[!INFO]
C3a is an anaphylatoxin
C3b is an opsonin (it binds to foreign molecules) -> it tags microorganisms as foreign.
Evolutionarily the newest but first to be discovered.
Evolutionarily the oldest
Basically, C3 is constantly being hydrolysed at low levels to form C3b but this is inactivated rapidly. If the C3b happens to bind to a pathogen, it become protected from inactivation and can trigger subsequent cascade activation.
The alternative pathway does not require antibodies.
It is triggered when C3b binds to bacterial polysaccharides and other endotoxins.
More details:
The alternative pathway of complement activation depends on spontaneous hydrolysis of C3 in plasma leading to the formation of C3 (H2O). This molecule binds to factor B. Subsequent activation by factor D results in the formation of C3 (H2O) Bb. This complex cleaves additional C3 to C3a and C3b constantly and at a low rate. In the presence of an activating surface (e.g. a bacterial wall), C3b is protected from inactivation by regulatory proteins like factor I and H. As a result, a more active alternative pathway C3 convertase - called C3bBb- is formed, which is further stabilized by properdin.Source
Then, the C3b particles formed by both pathways above goes on to form the C5 convertase by combining with various other complement factors.
[!INFO] C5 -> C5a (Most potent anaphylatoxin ) + C5b (initiator of MAC)
[!TIP] Mnemonic :
- some of these may help
- C1-INH - Hereditary aNg1odema (flipped HN1)
- C3 three rhymes with B(ee) for bacterial infections
- C5 – think five fails to thrive – Leiner's disease – malabsorption, diarrhoea, wasting, and dermatitis in children
- C5-9 – MAC – MeniNINEtis or MACingitis
Alternative pathway
classical pathway
MBL pathway
#2022BSQ-OCT/Q31
CPK = CK.
Creatine Kinase is a catalyst for the formation of ATP from ADP via transfer of phosphate from creatine phosphate (which is an energy reservoir for muscle.
It is a very good indicator of muscle breakdown and it's progression.
CPK is eliminated by the ❗Reticuloendothelial system❗. Serum level isn't elevated in kidney disease.
3 isoforms
Skeletal muscle - 99% CK MM
CK-MB = Usually in cardiac muscle. Can also be elevated in elite athletes and normal people after strenuous exercise (i.e can produce false +ve for MI)
CK is usually elevated in myopathies. => there are different types of myopathies
Can also be elevated in a few non myopathic conditions
We want to get urine samples which contain bacteria which have managed to enter the bladder. (bacteria colonize the distal urethra and genital mucosa)
Theoretical best sample is first voided urine of the day as bacteria have had time to multiply overnight and it is also the most concentrated sample.
Suprapubic taps should yield sterile urine in a healthy patient.
Prostatic massage should be done prior to urine sample correction in suspected if chronic bacterial prostatis is suspected. ❗Massage should be avoided in acute bacterial prostatits -> risk of bactiraemia!
Sample is cooled until it is sent to the lab to prevent bacterial multiplication affecting the colony count.
8 cells / microL = 2-5 cells per High power Field.
Very high associated with urinary infection.
White blood cell casts - renal infection = could be pyelonephritis.
Causes of sterile pyuria:
see [[SaltatoryConductionMechanism.png]]

Source: CVS physiology website.
| pacemaker cells | non pacemaker cells |
|---|---|
| No true resting potential | |
| Continuous action potentials generated | |
| Depolarization due to SLOW calcium current | FAST Na mediated depolarization |
| If or "funny current" is a mixed sodium/potassium inward current. |
#2020SBR-NOV/19
#2020BSQ-JUL/Q02
The pathophysiology of changes in hyperkalemia includes
Boradening of the QRS complex is a feature (although not mentioned in the table below) Source
| Level | Changes | Basis |
|---|---|---|
| 5.5 - 6.5 | 📑 Tall t waves | ❗ Repolarization abnormalities |
| 6.5 - 7 | 📑 P wave widening and flattening, broadening of PR interval | ❗Progressive atrial paralysis |
| 7.0 - 9.0 | 📑 Sinus brady, AV block, AF, conduction blocks | ❗Conduction abnormalities |
| > 9.0 | Sine wave | ❗Peri arrest |
In hyperkalemia, ECG changes progress from peaked T-waves to widened QRS and eventually to ventricular tachycardia, fibrillation or pulseless electrical activity arrest. These progressive changes can correlate with rising potassium levels. For example, peaked T waves might correspond with a potassium level of approximately 6 mmol/L, whereas cardiac arrest generally occurs at higher levels.
#2023SBR-NOV/Q24
read in K and C
Tall tented t waves - PR prolongation - Broad QRS - Sine wave pattern - asystole, VT, VF
Requires 1 - 2 hourly monitoring of plasma glucose.
[!INFO] Mnemonic: Opposite of the hyperkalemic changes
EKG changes can include
The 'classic findings' are
The U-wave is a deflection following the T wave. Potassium levels that are critically low (<1.7 mmol/L) can lead to torsades de pointes or “twisting of the points”, a polymorphic ventricular tachycardia.
[!INFO] 📑U wave
- mechanism of generation isn't clearly identified
- normal u wave is concordant with the t wave
- it is smaller than the t wave (1/3 size)
- it's size increases with decreasing hear rate
- Best seen in V2 and V3.
[!INFO] Definition of Tosade de pointes
Torsade is defined as the combination of polymorphic ventricular tachycardia plus a prolonged QT-interval.
Source
Polymorphic VT is defined as ventricular tachycardia with varying QRS amplitute.
Pathophysiology: QT prolongation predisposes to 'after depolarizations' which can produce TdP
also [[torsadesDePointes.png]]
Causes of QT prolongation:
| Congenital | Drugs | Other |
|---|---|---|
| - Jervell-Lange-Nielsen syndrome (includes deafness and is due to an abnormal potassium channel) - Romano-Ward syndrome (no deafness) |
- amiodarone, sotalol, class 1a antiarrhythmic drugs - tricyclic antidepressants, fluoxetine - chloroquine - terfenadine - erythromycin |
- electrolyte: hypocalcaemia, hypokalaemia, hypomagnesaemia - acute myocardial infarction - myocarditis - hypothermia - subarachnoid haemorrhage |
The most common EKG finding associated with hypercalcemia is shortening of the QT interval. In severe cases, Osborn or J waves might be seen or ventricular fibrillation might ensue. Recognition of these EKG findings can prompt urgent treatment.
The most common finding on EKG in patients with hypocalcemia is a prolonged QT interval.
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.105.166563
doi.org/10.1016/0002-9149(63)90255-8
#TODO
Hyponatremia and hypernatremia have no effect on the ECG.
Increased (hypernatremia) and decreased (hyponatremia) sodium levels do not have any effect on the ECG, nor cardiac rhythm, or impulse conduction. Source
#2021BSQ-JUL/Q31
[!TIP] GPT answer:
Certainly! Here is a list of common tumor markers and the tumors they are commonly associated with:
- Prostate-Specific Antigen (PSA) - Prostate cancer
- Carcinoembryonic Antigen (CEA) - Colorectal cancer, pancreatic cancer, lung cancer
- Alpha-fetoprotein (AFP) - Liver cancer, germ cell tumors, particularly testicular cancer
- CA-125 - Ovarian cancer (CA = carbohydrate antigen)
- CA 19-9 - Pancreatic cancer, colorectal cancer
- CA 15-3 - Breast cancer
- CA 27-29 - Breast cancer
- Human Chorionic Gonadotropin (hCG) - Germ cell tumors, particularly testicular cancer, ovarian cancer, ?lung CA
- Calcitonin - Medullary thyroid cancer
- Thyroglobulin - Thyroid cancer (papillary and follicular)
- Neuron-Specific Enolase (NSE) - Neuroendocrine tumors, small cell lung cancer
- Chromogranin A - Neuroendocrine tumors
- S-100 Protein - Melanoma, neuroendocrine tumors
- Human Epidermal Growth Factor Receptor 2 (HER2) - Breast cancer, gastric cancer
- Epidermal Growth Factor Receptor (EGFR) - Non-small cell lung cancer, colorectal cancer
- 5 HIA - carcinoid tumour
- Carcinoid tumors are of neuroendocrine origin and derived from primitive stem cells in the gut wall, especially the appendix.
BRCA1 and BRCA2 - breast and ovarian cancer.
[!TIP] A great summary!
Source
[!INFO] Differentiation of disease is vital to determine the potential effectiveness of surgery!
resection is curative in UC but disease recurs after resection in Crohn's;
Mnemonic: "Colectomy is curative"
| Feature | Crohn's Disease | Ulcerative Colitis |
|---|---|---|
| presentation | Abdominal pain + perianal disease. (although colonic disease can cause PR bleeding) | GI bleeding |
| Endoscopy | Cobblestones + linear ulcers | Diffuse continuous involvement, pseudopolyps |
| Radiography | Fistulae | No fistulae |
| Distribution | (potentially mouth to anus) Terminal ileal involvement Or ileocolitis, skip lesions(+) | No ileal involvement (backwash ileitis possible) |
| Rectal involvement | Possible, may spare the rectum | Rectum always involved |
| Pathology | Transmural involvement(+) (wall to serosa), Granulomas (+) | mucosal and submucosal inflammation |
| Serositis(+), Creeping fat | Crypt abscesses – Crypt abscesses are more common in UC than CD | |
| Management | Resection not curative | Colectomy eliminates illness |
| Epid | Develops in teen and twenties | |
| Complications | Intestinal obstruction / perforation | |
| Extraintestinal manifestations | Toxic megacolon! | |
| Malabsorption (because UC involes only the colon) | ||
| Smoking effect | Increased by smoking | Reduced by smoking! |
| Appendisectomy | Increases risk of CD | Protective against UC (mnemonic: appendix connected to the colon) |
[!INFO] NOTE! Crypt abssesses are present in both but more common in ulcerative colitis.
Peak incidence for both is between 15-30 years. But disease can occur at any age.
Research shows smoking – specifically the chemical nicotine in tobacco – seems to both guard against ulcerative colitis (UC) and help ease symptoms.
[!INFO] 'Positive features' of Ulcerative colitis not seen in Crohn's disease
- Toxic megacolon can occur.
- Marked pseudopolyps
- ? More malignant potential
- Rectal involvement is always present
- ❗primary sclerosing cholangitis (seen mostly with UC)
- more likely to develop pyoderma gangrenosum
Apparently, ulcerative colitis is associated with thrombocytosis. #2020SBR-JUL/Q12
In Ulcerative colitis, weight loss is a feature only of severe disease.
Weight loss appears to be more common in Crohn's disease.
You'd expect that to be due to malabosorption but megaloblastic anaemia is 'unusual' in crohn's disease (and UC doesn't involve the small intestine anyway) -> ?probably due to systemic effect of chronic inflammation.
?UC patients may be more likely to have blood in the stool.
#2021SBR-NOV/Q08
Extraintestinal manifestations are common to both diseases.
Joint complications are the most common:
Ileal resection can cause bile acid malabsorption -> diarrhoea.
Goal of treatment is to prevent recurrences and promote healing of existing lesions.
Except for steroids, the others can be used for maintenance.
#TODO
#2021GM-JUL/Q39
[!TIP] PBC - the C can stands for Cirrhocis or Cholangitis.
[!TIP] When to suspect
Suspect in a middle aged woman with pruritus who has elevated ALP and possibly other autoimmune conditions.
[!TIP] Mnemonic: Don't confuse with PSC - PBC has 'cirrhosis' in the name -> liver tissue is inolved -> interlobular bile ducts are involved.
Middle aged, itchy woman - Karens
ALP is the only abnormal investigation
MCQ Discussion:
Most often diagnosed through routine screening.
❗Usually asymptomatic. -
But Fatigue is a prominent presenting symptom. Pruritus is an early and common sign. Icterus is late signs.
95% of PBC occurs in women aged 40 - 50 years.
There is destruction of small interlobular bile ducts.
Antimitochondrial antibodies are found in all patients. M2 is specific for PBC.
The presence of serum antimitochondrial antibodies (AMA) is a highly specific indication of primary biliary cirrhosis (PBC).
Presentation: Asymptomatic with #hepatomegaly and raised ALP. (raised ALP is often the only abnormal investigation)
In Primary Biliary Cirrhosis, the level of ALP is generally greater than that of GGT. In this case, transaminases are invariably normal or only minimally elevated.Source
Pruritus and fatigue.
Raised cholesterol and Xanthelasma
Associated with many autoimmune conditions.
Also associated with RTA. - but ?rare
#2022BSQ Q49
Types of immunoglobulins and antibodies
IgG IgA IgD IgM IgE
Source
#2022BSQ-OCT/Q40
Animal based : not commonly used.
Bovine insulin differs from human by 3 amino acids, porcine by 1 amino acid.
Regular insulin and NPH insulin are considered older insulins.
Their time to peak and duration of action don't mimic physiologic secretion.
❗(U-100) denotes the usual concentration (100 U/ml).
Duration: Intermediate.
Suspension of human insulin, protamine and zinc. -> delays release of insulin into blood, also longer time to peak.
Patient must eat after the morning dose is given, to avoid hypoglycaemia.
mix immediately before injection and given at room temperature.
NPH insulin is a cloudy solution.
Can be mixed with regular or rapid acting insulins in the syringe.
Always draw up the regular(clear) insulin first to avoid contaminating the regular insulin with isophane insulin, thereby altering its pharmacokinetics.
Not regularly used nowadays, partly because of the advent of DPP-4 inhibitors.
made by recombinant DNA technology.
Substitution of amino acids produces rapid acting and long acting analogs.
Lispro, aspart, glulisine (and faster aspart, lipro-aabc)
Duration: (very short) duration and rapid onset
modifications were made in the insulin molecule to prevent it from forming hexamers or polymers that slow absorption and delay action
Insulin aspart- substitution of aspartic acid for proline at position B28.
Insulin lispro is identical to human regular insulin except for a lysine and proline at positions B28 and B29.
Insulin glulisine has a lysine and glutamic acid at positions B3 and B29 respectively.
Rapid acting insulins are more convenient.
U-200 lispro and U-200 lispro-aabc, are high concentration preparations which have some niche use cases.
Insulin detemir – Detemir is an acylated insulin; the fatty acid side chain allows reversible albumin binding as well as concentration-dependent self-association (ie, formation of dihexamers) that results in prolongation of action.
Determir is much less potent - so it is formulated in a 4:1 ratio. (1 Unit of determir contains four times as many insulin molecules as any other preparation of insulin)
❗Can't mix with rapid acting insulins.
Glargine is identical to human insulin except for a substitution of glycine for asparagine in position A21 and by the addition of two arginine molecules to the amino terminus.
After subcutaneous administration, glargine precipitates in the tissue, forming hexamers, which delays absorption and prolongs duration of action.
Glargine, which is in an acidic solution, cannot be mixed with rapid-acting insulins, as the kinetics of both the glargine and rapid-acting insulin will be altered
Glargine has less nocturnal hypoglycemia than NPH insulin
Duration of action : 24 hours but some may need twice daily dosing as half life is 12 hours. Unlike glargine, determir has a small peak in it's concentration profile.
Higher concentration preparations of glargine (U-300) have an even flatter concentration curve with lower hypoglycaemic effect.
form multimers from which monomers are release-> even longer duration of action.
Can mix with rapid acting insulins.
[!TIP] Degludec - the only long acting insulin that can be mixed with rapid acting insuline Mnemonic: Glue - glue it up.
Site of injection - Limbs are faster than abdomen. (muscle-> increased blood flow)
NPH insulin - leg or buttock preferred for moderate rate of absorption.
Pre meal regular insulin - abdominal wall preferred for rapid absorption.
The absorption of the long-acting basal insulin analogs, glargine and degludec, do not appear to be significantly influenced by injection site
#2020BSQ-JUL/Q25
This Source and other articles in general seem to indicate that basal bolus regimes are too rigorous to follow for elderly people.
Morning basal insulin regimens may be recommended. Usually, for fasting hyperglycaemia, nocturnal basal dose is given.
#2022BSQ Q48
#2022BSQ-MAY Q46
Hypersensitivity reactions refer to undesirable responses produced by the normal immune system - Source
[!INFO] Mnemonic
Type III - 3rd letter in alphabet - C for immune complexes.
[[Toxicology#Serum sickness]]
| Type 1 | Type 2 | Type 3 | Type 4 |
|---|---|---|---|
| commonest type | Goodpasture syndrome, autoimmune anaemias, erythroblastosis faetalis | [[2023-SEMPaper#Systemic Lupus Erythematosus SLE|SLE]], serum sickness, reactive arthritis, PSGN, [[2022 November SBR#Rheumatoid arthiritis|Rheumatoid Arthtiris]] | second most common |
| Immediate hypersensitivity - eg analphylaxis | 2-24 hours | days to weeks | 2 days |
| IgE (from plasma cells) mediated | IgG and IgM - bind to own cell surface molecules -> complement activated | IgG and IgM antigen antibody complexes | Cell mediated - non antibody dependant - T cells, monocytes and macrophages |
| degranulation of mast cells and basophils | complement mediated red cell agglutination and other cell lysis | Cytokines which cause cell death and inflammation are released | |
| Type | Alternate name | Examples | Mediators |
|---|---|---|---|
| I | Allergy (immediate) | • Atopy – Anaphylaxis – Asthma – Allergic rhinitis – Angioedema – Food allergy | IgE |
| II | Cytotoxic, antibody-dependent | • Erythroblastosis fetalis • Goodpasture syndrome • Autoimmune anemias, thrombocytopenias | IgG, IgM |
| III | Immune complex disease | • Systemic lupus erythematosus • Serum sickness • Reactive arthritis • Arthrus reaction | Aggregation of antigens IgG, IgM Complement proteins |
| IV | Delayed-type hypersensitivity, cell-mediated, antibody-independent | • Contact dermatitis • Tuberculosis • Chronic transplant rejection | T cells, monocytes, macrophages |
Is when the produced antibodies have the property of stimulating receptors on cells. Best example is Grave's disease.
Source
[!TIP] Hypersensitivity Vs Autoimmune disease
Hypersensitivity is an abnormal immune response to a harmless stimulus. When the 'stimulus' is a self antigen, we call it autoimmunity.Autoimmune diseases can be classified in the same way as hypersensitivity conditions. but IgE is not involved in autoimmunity.
so in the table[[2022 November SBR]] below, there is no "type I" in the autoimmune categories
Autoimmune diseases caused by antigens against cell surface receptors: [[moreAutoimmuneDiseases.png]]
#2022BSQ Q54
| Infection | Typical presentation |
|---|---|
| Escherichia coli | Common amongst travellers Watery stools Abdominal cramps and nausea |
| Giardiasis | Prolonged, non-bloody diarrhoea |
| Cholera | Profuse, watery diarrhoea Severe dehydration resulting in weight loss Not common amongst travellers |
| Shigella | *Bloody *diarrhoea Vomiting and abdominal pain |
| Campylobacter | A flu-like prodrome is usually followed by crampy abdominal pains, fever and diarrhoea which may be bloody May mimic appendicitis Complications include Guillain-Barre syndrome |
| Amoebiasis | Gradual onset bloody diarrhoea, abdominal pain and tenderness which may last for several weeks |
| Staphylococcus aureus | Severe vomiting Short incubation period |
| Bacillus cereus | Two types of illness are seen - vomiting within 6 hours, stereotypically due to rice - diarrhoeal illness occurring after 6 hours |
| #2016GM-OCT/Q30 |
[!TIP] The types of E coli - "HIT"
enterohaemorrhagic (EHEC) (aka STEC - shiga toxin producing E coli)
enteroinvasive (EIEC)
enterotoxigenic (ETEC)
The first two cause bloody diarrhoea.But there are actually 5 types.
- ETEC causes watery diarrhea in resource-limited settings and is commonly found in food and water in areas without adequate sanitation
- EPEC (enteropathogenic) was the first E. coli pathotype identified as a causative agent of watery diarrhea primarily in infants and young children in resource-limited settings
- EAEC (enteroaggregative) is a causative organism of acute and chronic watery diarrhea in resource-limited and resource-rich regions
- EHEC/STEC produces Shiga-toxin and includes serotypes O157:H7, as well as others
- EIEC-induced diarrheal illness is uncommon due
[!INFO] A Great table!
[[diarrhoeaInResourceRichSettings.png]] <- A great table!
[!TIP] Watery diarrhoea
"Noninflammatory diarrhea is caused by the action of enterotoxins on the secretory mechanisms of the mucosa of the small intestine, without invasion" - Medscape.Same day:
- Norovirus (mnemonic : N for 'naught' for day zero) ("winter vomiting bug" - also causes vomiting)
- clostridium perfringens
- possibly listeria (pregnancy, immunosuppression, extremes of age)
Next day:
- E coli - enterotoxigenic
- most other viruses - (1-3 days) diarrhoea in children, immunocompromised adults
- (including Rotavirus)
Same week
- [[Misc infectious diseases#Cyclospora cayatensis infection|Cyclospora infection]]
Weeks later
- Giardia 1 to 2 weeks later - day care, swimming pools, travel / camping.
- Cryptosporidium 2-28 days (upto 1 month after) - Associated with day care centers, swimming pools. (common in HIV patients)
- see [[HIV-AIDS#Selected aids defining illnesses]]
^5eaea3
[!TIP] Mnemonics: inflammatory diarrhoea
Fever, mucoid or bloody stools show infective diarrhoea:
"Can't Assume Everyone's Your Very Special Sidekick"
Let's break it down:
- "Can't" - Campylobacter
- "Assume" -[[2023-SEMPaper#Amoebiasis|Amoebiasis]]
- "Everyone's" - E. coli
- "Your" - Yersinia
- "Very" - Vibrio parahaemolyticus
- "Special" - Salmonella
- "Sidekick" - Shigella
Most of these have P-incu of 1-3 days.
But, entamoeba - much longer- 1 to 3 weeks, yersinia - slightly longer- 4-6 days, E-coli 1-8 days.
Complications of dysentery include [[General medicine 3#Guillain barre|GBS]], [[2022-SBR-MAY#Reactive arthritis]]
[!INFO] Giardiasis is one of the most common intestinal infections worldwide in both developed and developing countries
Main two pathogens of epidemic diarrhoea
Commonest causes of non epidemic watery diarrhoea - E. coli.
[!TIP] mnemonic
Acute bloody diarrhoea
$$
{C^1S^2E^3}
$$
Commonest cause of non epidemic bloody diarrhoea - shigella flexneri (not dysenteriae)
#2021BSQ-NOV/Q37
Symptoms suggesting diarhoeal illness caused by preformed toxins:
#2020BSQ-NOV/Q50
[!INFO] How to understand the life cycle;
parasite has a free living cycle and parasitic cycle.
So adult worms can be found in the environment and the intestinal lumen of hosts.
Eggs can be deposited a) In the host intestine and b) in the environment.
Eggs always produce rhabditiform larvae.
Eggs -> rhabditiform larvae -> filariform larvae. (Infective stage) (autoinfection or otherwise).
If excreted with stool, rahbditiform larvae can go on to develop into adult sexual stages which produce more eggs in the free living cycle.
Female Adult worm (who live embedded in the submucosa of the small intestine) lays eggs.
It has been thought that the L3 larvae migrate via the bloodstream and lymphatics to the lungs, where they are eventually coughed up and swallowed. However, L3 larvae appear capable of migrating to the intestine via alternate routes (e.g. through abdominal viscera or connective tissue)
Respiratory : Dry cough - about 1 week after infection
Abdominal pain, bloating, intermittent constipation and diarrhoea - about 3 weeks or later after infeciton (due to infection of the small intestine)
Skin: Itchy rash at site of entry; recurrent red rash along thighs and buttocks. - Larva currens (pathognomonic of Strongyloidiasis).
Disseminated life threatening infection can occur in immunosuppressed people.
Eosinophilia(+).
Can cause [[2021-SBR-November#Loffler syndrome / Loeffler syndrome | Loeffler syndrome]]
Ivermectin has been shown to be superior to albendazole.
Ivermectin: binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate muscle and nerve cells of microfilaria.
Albendazole and other similar drugs inhibit the beta tubulin of worms (intracellular cytoplasmic structural protein) -> immobilization and death.
#2020BSQ-NOV/Q50
? Dog tape worm
A 2-7mm long small tape form whose definitive host is the dog.
Intermediate host is animals like sheep.
Sheep tissues have cysts which are infective when ingested by a dog.
The adult forms in the dog then shed eggs with faeces which are usually ingested by the sheep, but can also be ingested by humans.
One ingested, the eggs hatch the the larvae penetrate the intestinal wall and take up residence in the tissues.
In the tissues, they from hydatid cysts.
The cysts usually grow for many years and are asymptomatic until they cause symptoms due to pressure effects.
However, if a cyst ruptures, it can cause analphylaxis, or a milder fever, and dissemination of the parasites within.
Treatment: Surgery or less invasive procedures like PAIR (percutaneous aspiration, injection of chemicals and reaspiration).
[!TIP] Sheepdog
#2020BSQ-NOV/Q50
Image of skeletal muscle encysted and liberated trichinella parasite.
Treatment:
Albendazole and mebendazole for about 14 and 10 days respectively. Treatment should be started within first few days of infection, or else, larvae will migrate into skeletal muscle and treatment will not completely eliminate the infection.
Trichiuris trichiura - the human whipworm
[!INFO] Delayed action "haal atey"
Diagnosis:
Treatment:
Treatment:
#2022BSQ Q51
Skull base fracture and associated injuries; Source
NCBI article <- good link
Cranial nerve injuries: Page 1079 of Moore's clinical anatomy.
Posterior fossa signs: battle signs, haemotympanum, loss of gag reflex and accessory nerve palsy.
#2022GM Q14
#2021GM-JUL/Q17
[!TIP] Mnemonic
SR4 : Sjogrens => RoLa+ / RF+ / RTA / Raynaud
Pathogenesis: Autoimmune disease affecting exocrine glands.
In most cases, Sjogren syndrome is only 'irritating' and not dangerous.
Can occur as a primary disorder or secondary to another rheumatic disease.
Symptoms are classified mainly as
Mild disease : just dry eyes and mouth; Requires diagnostic criteria to be fullfilled to diagnose SjD.
Severe disease:
A severely affected patient may have florid salivary gland enlargement, adenopathy, antibodies to the Ro/SSA and La/SSB antigens, cryoglobulinemia, hypocomplementemia, a propensity to develop non-Hodgkin lymphoma, and other extraglandular disease manifestations.
90% are positive for Rheumatoid factor: Kumar and Clark
Epidemiology: Most Commonly occurs in women aged 50-60 years old.
Keratoconjuntivis sicca - term for the occular manifestations of Sjogrens.
Mikulicz syndrome: Parotid and lacrimal gland enlargement;
Biopsy showing focal lymphocytic infitrate of labial salivary glands. Termed Focal lymphocytic sialadenitis.
Objective test: Focal lymphocytic sialadenitis score >= 1;
Anti Ro/SSA and anti La / SSB positivity suggests Sojgren's disease.
Background of systemic autoimmune disease. -
The most common associations are SLE and Rheumatoid arthritis.
#2020SBR-JUL/Q18
This flow chart shows the mechanism of activation of various vasoactive systems in cirrhosis.

Several haemodyanic and vascular changes occur which contribute to the formation of cirrhocis.
Vascular:
Multiple mediators have been studied as sources of the systemic vasolidation but the most important one seems to be increased NO synthesis.
inhibition of synthesis of NO in rats restores normal arterial pressure.
? cause for increased NO
Portal hypertension -> increased portosystemic shunting -> decreased hepatic clearance of bacterial toxins / DNA absorbed from GI tract.
mediated by vascular changes:
Splanchnic vasodilation
Renal artery vasoconstriction
(and also pulmonary vasodilation)
Ascites: The pathological accumulation of fluid in the peritoneum.
Development of portal hypertension is the first step and is essential for the formation of ascites in cirrhocis.
Older theories of ascities formation : undefill theory and overflow theory. Modern arterial vasodilation hypothesis fits better with data.
A portal pressure >12 mmHg appears to be required for fluid retention
Portal hypertension is not simply due to mechanical obstruction of the portal system. It occurs due to increased flow from the splanchnic arteries.
See hypothesis-highlights on UpToDate
#2022GM Q32
Serum 'to' Ascites Albumin gradient
SAAG > 11g/L - low protein in ascitic fluid => Suggest portal hypertension as cause; (i.e transudate)
SAAG < 11g/L - high protein in ascitic fluid (or low serum protein) => Exudate (?malignancy)
❗Low ascitic fluid protein may increase the risk of SBP as there are no opsonins in the fluid to combat infection.
#2020SBR-JUL/Q18
Measures to reduce ascites:
In general, the goal of diuretic treatment of ascites should be to achieve a weight loss of 300-500 g/d in patients without edema and 800-1000 g - MedScape
#2022GM Q21
#2017GM-OCT/Q10
Respiratory epithelium - ciliated pseudostratified columnar epithelium.
Note the presence of smooth muscle and it's decreasing thickness as the airways become smaller.
Bronchioles - intralobular airways < 1mm in diameter arising roughly after the 10th generation of branching.
Commoner in women.
Increases with age; marked increase after 60 years.
Bronchiectasis is the permanent dilation of bronchi and
bronchioles caused by destruction of the muscle and the
supporting elastic tissue, resulting from or associated with
chronic necrotizing infections. It is not a primary disease
but rather secondary to persisting infection or obstruction
caused by a variety of conditions
Once patients develop bronchiectasis, most commonly isolated organisms are haemophillus and pseudomonas and streptococcus pneumoniae.
Obstructive impairment (ie, reduced or normal FVC, low FEV1, and low FEV1/FVC) is the most frequent finding on spirometry. ;
$$
\LARGE{Obstruction = ↓\frac{FEV_{1}}{FVC}}
$$
See [[Lung function tests#Obstructive vs. restrictive diseases]]
Clinical and CT:
CT features that are reliable signs of bronchiectasis:
Obstruction - tumour, lymph nodes, aspiration etc. <- impaired drainage
Inherited disorders -
Cystic fibrosis #autosomal-Recessive <- impaired clearance of mucous
Kartagener syndrome <- Ciliary impairement
Autosomal recessive #autosomal-Recessive
Situs inversus, chronic sinusitis, and bronchiectasis; Underlying pathology is primary ciliary diskinesia. Kartagener Xn is a subset of primary ciliary diskinesia (in which patients may not have situs inversus).
Screening test -> patients have low levels of nasal nitric oxide.
Immunoglobulin deficiencies <- recurrent infection
Necrotizing of suppurative pneumonia - staph aureus or klebsiella <- scarring and impaired clearance; ?exagerrated neutrophil response
Young syndrome - similar to CF but no evidence of CF; rare diagnosis nowadays.
Associated with two rheumatic disorders - Sjogren syndrome and Rheumamtoid arthritis.
[[General Medicine 1#Allergic bronchopulmonary aspergillosis|Allergic bronchopulmonary aspergillosis]] - ? central bronchiectasis
Antibiotics for exacerbations
Control of acute bleeding with bronchoscopic local therapy or bronchial artery embolization.
Refractory disease: surgical therapy - ? resection
#2022BSQ-MAY/Q49
| Defect | Presentation |
|---|---|
| Antibody deficiency | Recurrent sinopulmonary infection / meningitis / chronic GI infections (esp. capsulated organisms - H. Influenza, N. meningitidis, S. pneumonae) |
| Granulocyte (neutrophil) defects | Recurrent soft tissue infection |
| Cell mediated immunity (esp. T cells) | Infection with Viruses, intracellular pathogens, fungi (CMV, EBV, mycobacteria, candida, [[HIV-AIDS|cryptococcus]],[[HIV-AIDS#Pneumocystic jirovecii pneumonia|pneumocystis]] ) |
Skin infections, in isolation, are not usually indicative of an underlying primary immunodeficiency.
Chronic mucocutaneous candidiasis - ussually begins in childhood; associated with several immunodeficiency states; usually doesn't show systemic infection with the fungus.
Recurrent herpevirus infection / reactivation -> These individuals should be evaluated for underlying T or natural killer (NK) cell dysfunction. See -> [[2021 Basic Sciences July#Natural killer cells]]
***
However, recurrent respiratory tract infections in combination with more serious infections are a classic presentation of antibody deficiencies.
***
~~>
- Isolated urinary tract infections are more suggestive of anatomic defect than immunodeficiency.
- Relapsing, recurrent, and/or progressive enterocolitis due to common enteropathogens, such as Giardia, enteroviruses, cytomegalovirus, and campylobacter, are associated with underlying hypogammaglobulinemia and/or T cell immunodeficiency.
- Recurrent Neisseria meningitidis meningitis -> Deficiency of one or more of the terminal complement components (C5, C6, C7, C8, C9) . Low complement levels may be due to either congenital complement deficiency or acquired diseases, such as systemic lupus erythematosus.
- Immunoglobulin deficiency disorders or impaired reticuloendothelial function resulting from splenectomy or hemoglobinopathy are associated with an increased risk of bacteremia and meningitis due to encapsulated pathogens.
- Marked elevation of serum IgE with multisystem infections -> Job syndrome
~~
| Defect | Outcome | Organism |
|---|---|---|
| low gamma globulin | recurrent enterocolitis and ? sinopulmonary infections | Giardia, enteroviruses, CMV, campylobacter |
| Terminal complement | Recurrent neisseria meningitis | |
| Ig or RET | Recurrent encapsulated pathogen infection | |
| Selective IgA deficiency | Usually asymptomatic; can present with recurrent mucosal pyogenic infections |
Usually due to defects in B lymphocytes -> not enough antibodies produced.
Recurrent sinopulmonary infections and persistence of gut pathogens.
Leads to bronchiectasis and chronic diarrhoea with malabsorption.
[!INFO] Commonest significant antibody deficiency affecting children and adults.
Diagnosed at: 20 and 45 years of age.
? etiology - few are inherited. Pattern may by #autosomalDominant with low penetrance or #autosomal-Recessive - UpToDate
There is
Complications:
Chronic giardia infections with malabsorption can occur.
Treatment is IVIG.
Commonest primary immune deficiency.
Individuals are usually asymptomatic. -> treatment is only antibiotics as needed.
Can present with recurrent mucosal pyogenic infections.
#2021BSQ-JUL/Q24
Also called hypogammaglobulinaemia.
Mutation of the BTK gene impairs B cell maturation -> causes low or absent mature B cells -> severe hypogammaglobulinaemia.
Commonest inheritance: #x-linked-recessive with mothers being carriers. #autosomal-Recessive inheritance is seen in ? 50%. - confirm
Manifestation: recurrent sinopulmonary infections.(From 6 to 12 months of age, otitis media, sinusitis, bronchitis, and pneumonia).
Common pathogens: Encapsulated pyogenic bacteria Haemophillus influenzae and strep pneumoniae.
Treatment: repeated IVIG transfusions or stem cell transplant.
[[2022-November#Complement system overview]]
Impaired alternative pathways -> non specific impairement -> bacterial infections.
Impaired classical pathway -> increased infection and increased immune complex deposition -> SLE, vasculitis, glomerulonephritis etc.
MAC -> neisseria infections.
#2022BSQ-MAY/Q49
- persistent and recurrent diarrhoea, otitis media, thrush, and respiratory infections
[[ImmuneResponsesTofungalpathogens.pdf]]
Not as well understood as bacteria and viruses.
Pattern recognition receptors (PRR) on antigen presenting cells are triggered by fungal cell components.
This causes intracellular signalling of the APC which promotes phagocytosis and stimulates killing mechanisms.
The adaptive immunity to fungi is mediated by CD4+ Th1 cells with produce interferron gamma and CD4+ Th17 cells which produce IL-17. They drive killing by innate effector cells like marcophages and neutrophils.
So overall,

[!INFO] presentation
> Is with recurrent and severe bacterial (Staphylococcus, pseudomonas, salmonella, Nocardia) and fungal (candida, Aspergillus) infections, most commonly of the respiratory tract and skin.
#2020BSQ-JUL/Q29
Splenectomy leaves the patient vulnerable to infection by capsulated organisms.
[!TIP] Mnemonic: Capsulated organisms : Have No Sex.
More than half of those with OPSI die.
Encapsulated organisms are resistant to phagocytosis without opsonization.
❗The spleen is a major site of early IgM production.
IgM memory B cells produce IgM to promote the clearance of polysaccharide-encapsulated bacteria.
Although the total B lymphocytes remain intact, a significant fall in the levels of memory B cells and switched B cell proportions are usually encountered 150 days post-splenectomy. This acts as a particular predisposition to infections caused by polysaccharide-encapsulated bacteria and is responsible for a diminished immunological response to polysaccharide vaccines
Source
However, even after opsonization, the bacteria must be phagocytosed. Splenic macrophages are a major contributor to this phagocytosis.
So in asplenia, there is impaired IgM production and thus opsonization and also impaired phagocytosis.
[!INFO] primary Vs. secondary immune response:
Source
#2019BSQ-OCT/43
"Amyloid" was meant to describe the starch like properties of the substance. Initially described as "waxy" and "lardaceous".
Normally soluble proteins are deposited extracellularly as beta pleted fibrils.
There are 18 different types of systemic and 22 localized forms of amyloidosis
The four most common causes of systemic amyloid deposition are
[!INFO] AL Vs AA : importance of differentiating
AL amyloidosis must be differentiated from other forms of amyloidosis (eg, AA amyloidosis, ATTRmt amyloidosis, and ATTRwt amyloidosis) since the latter are non-neoplastic and will not benefit from chemotherapy.
| Type | Constituent |
|---|---|
| AL Amyloidosis | Deposition of Ig Light chain fragments |
| Transthyretin amyloidosis | |
| AA amyloidosis | serum amyloid protein - acute phase reactant; Most common form in resource limited countries - occurs due to chronic inflammation |
Other forms of amyloidosis:
Histological : Fat pad biopsy (less risk of bleeding)
Organ biopsy is needed if a specific organ is involved.
When Congo red stains binds to amyloid protein, it produces apple green birefringence.
Looks similar to DM nephropathy but the staining characteristics are different (DM nephropathy is PAS and silver stain positive)
[!INFO] MGUS to myeloma
- All patients with active myeloma once had MGUS but
- Only 20% of patients with MGUS actually progress to active myeloma.
- The risk of a patient's progression from MGUS to active myeloma is only 1% per year. Source
AL amyloidosis is Associated with plasma cell dyscrasia (multiple myeloma, waldenstrom macroglobulinemia)
There is multisystem amyloid deposition
Fatigue, non intentional weight loss
📑Heavy proteinuria (70%) - nephrotic syndrome
📑oedema
#hepatosplenomegaly (hepatomegaly +/- splenomegaly seen in 70%)
Cardiomyopathy and heart failure (60%) - thickening of interventricular septum is present / 📑MI due to accumulation of amyloid in coronaries.
Neuropathies - carpal tunnel, mixed sensory and motor peripheral neuropathy is a prominent feature in AL amyloidosis. (Symptoms of numbness, paresthesia, and pain are frequent)
📑Amyloid infiltration of muscles - macroglossia with scalloping and shoulder pad sign. (also enlarged deltoids)
Skin - purpura (raccoon eyes with valsalva maneuver is specific), waxy skin, easy bruising.
📑Coagulopathy - possibly due to factor X binding of coagulation factors to amyloid.
📑GI involvement: gastroparesis, constipation, bacterial overgrowth, malabsorption, and intestinal pseudo-obstruction resulting from *dysmotility
Bortezomib based induction <- a myeloma directed therapy
Melphalan
Haematopoietic cell transplantation.
This disorder has a poor long-term prognosis, with cardiac or hepatic failure, and infection being the major causes of death
Earlier detection confers better outcome.
The most common organ affected by AA amyloid is the kidney (approximately 80 percent of patients -> causes nephrotic syndrome.
Seen in Chronic inflammatory disorders include rheumatoid arthritis, inflammatory bowel disease and untreated familial Mediterranean fever.
AA amyloidosis may complicate chronic diseases in which there is ongoing or recurring inflammation, such as rheumatoid arthritis (RA), spondyloarthritis, or inflammatory bowel disease; chronic infections.
SImilar to AL (but cardiomyopathy is rare)
GI involvement: similar to AA amyloidosis
In untreated patients, AA (secondary) amyloidosis carries a significant risk of mortality due to end-stage kidney disease, infection, heart failure, bowel perforation, or gastrointestinal bleeding.
Successful treatment of the underlying inflammatory process improves kidney function.
Treatment of the underlying condition can control but not cure amyloidosis.
For transthyretin type amyloidosis, liver transplant is definitive therapy as the liver is where transthyretin is made.
Spondylos = greek for vertebrae
Uveitis
The presence of leukocytes in the anterior chamber of the eye is characteristic of anterior uveitis.
The presence of leukocytes in the vitreous humor - intermediate uveitis
Evidence of active chorioretinal inflammation -> posterior uveitis
Sacroiliac joint:
Syndesmophytes and changes of spondylitis in the spine, which are most often detected in more longstanding disease.
A syndesmophyte is a bony growth originating inside a ligament, commonly seen in the ligaments of the spine, specifically the ligaments in the intervertebral joints leading to fusion of vertebrae.
Inflammatory osteoproliferative lesions in the spine are called syndesmophytes (marginal and non-marginal), and degenerative osteoproliferative lesions are called osteophytes. Syndesmophytes are more vertically oriented than osteophytes.
| Syndesmophyte | Osteophyte |
|---|---|
| Arise from calcification withn ligaments | Arise from bone (vertebral bodies) |
| Seen in inflammatory (spondylo) arthropathies | See in Osteoarthritis |
| Source |
[!TIP] Mnemonic: RePsAnkIb
- Reactive
- Psoriatic
- Anky spondylos
- IBD associated
[!INFO] Mnemonic: PAIR
Mnemonic for spondyloarthritis : PAIR ->
#2022GM Q25
#2022GM Q27
Ankylosing = stiffness or fixation of a joint by disease
Affects teens to early 30s, male >> female (5:1).
Pathology: lymphocyte and plasma cell infiltration of the attachments of ligaments. (enthesitis)
Some terminology: not super important
SourceGreat article!
HLA-B27
[!INFO] Key points
- It's largely a genetic disease - Patient's children have increased risk of getting it
- Pathogenesis consists of inflammation, bone erosion and syndesmophyte formation.
- Bone erosion and syndesmophyte formation are probably not linked to inflammation
- TNF-blockage suppresses symptoms but doesn't arrest bone changes.
[!TIP] mnemonic:
Extra-articular complications all begin with A:
- Apical fibrosis
- Anterior uveitis
- Aortic regurgitation
- Achilles tendonitis
- AV node block
- Amyloidosis
-passMedicine
"Plain x-ray of the sacroiliac joints is the most useful investigation in establishing the diagnosis."
The sacroiliac joint is actually a synovial joint with hyaline on the sacral surface and fibrous cartilage on the iliac surface Source.
#2022GM Q30
Congenital
Acquired
Hepatosplenomegaly and lymphadenopathy are rare.
[!TIP] Mnemonic : BPH - bradykinin, prostaglandin and histamine act together.
| | |
[!INFO] Up to 1 year post op for valve replacement, staph epidermidis >> staph aureaus.
[[aetiologicAgentsInfectiveEndocarditis.png]]
HACEK denotes Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella kingae.
- They are also some of the oldest antiepileptics. Newer drugs have better pharmacokinetics.
- The narrow spectrum AEDs mostly work for specific types of seizures (such as focal, absence, **or** myoclonic seizures).
- Broad spectrum AEDs additionally have some effectiveness for a *wide variety of seizures* (focal **plus** absence myoclonic seizures).
Source
- Mnemonic: cOllECtIvE (COLLECTIVE IS SIMILAR TO 'BROADLY') (LeCo-VoLT)
Treatment: See [[#Treatment for GAD and panic disorder]] below.
Source
PD is defined by the DSM-5 as recurrent panic attacks that include characteristic symptoms and lack an obvious trigger followed by concern about another attack lasting for at least 1 month.
Panic attacks that are nocturnal or lack fear require a more extensive workup.
Commonest symptoms is palpitations.
"panic attack": an intense surge of fear or discomfort which peaks within minutes which are associated with many physical symptoms including chest pain.
If > 8 hours since ingection, NAC is given rather than methionine.
[!INFO] Paracetamol
1,4,8,16
Gastric lavage 1 hour.
Activated charcoal 4 hours. Levels also at 4 hours.
Before 8 hour, methionine can be given and is as effective as NAC.
After 8 hours, give NAC.
Liver damange unlikely if NAC started within 8 hours.
Arterial pH < 7.3, 24 hours after ingestion
or all of the following:
respiratory alkalosis – hyperventilation (in early stages with high salicylate levels)
metabolic acidosis – lactate
hypokalemia
Management
supportive
alkaline diuresis was used earlier
almost identical to cinchonism (quinine toxicity).
#2022SBR-MAY/Q16
#2016GM-APR/Q05
SLUDGE/BBB – Salivation, Lacrimation, Urination, Defecation, Gastric Emesis, Bronchorrhea, Bronchospasm, Bradycardia, and Miosis
- Mainly Proximal Muscle weakness: characteristic neurological findings including neck flexion weakness, decreased deep tendon reflexes, cranial nerve abnormalities, proximal muscle weakness, and respiratory insufficiency
- Complete resolution occurs in 2-3 weeks if the patient receives ventilatory support
- Intermediate syndrome is rarer with carbamate poisoning Source but it can occur.
Several weeks after exposure
Characterized by distal weakness and sensory loss first in the lower limbs; may progress proximally and affect upper extremities.
This occurs due to inhibition of neuropathy target esterase (NTE) by organophosphates.
Carbamates are generally though to not cause neuropathy because the acetylcholinesterase bone is reversible- but some cases have been reported. Source
| Feature | Hepatitis B | Hepatitis C |
|---|---|---|
| Epidemiology | est. 220 million carriers | est. 70 million carriers |
| Virus type | DNA | SS-RNA |
| Transmission | Vertical(during birth) is common Hep B in children is a main issue |
Vertical transmission is rare |
| Blood + products | Blood + products, needle sharing | |
| Vaccine | Present | Rapid mutations -> No vaccine |
| Clinical course | Acute: 70% subclinical (anicteric) 30% icteric hepatitis 1% - fulminant hepatitis Overall, in vast majority disease is self limited. |
Acute: Asymptomatic but 10% will have flu like symp. Overall about 25% will clear the infection spontaneously. |
| Chronic: 5% of acute infection becomes chronic | Chronic: 90% of asymptomatic acute infection becomes chronic. 50% of symptomatics become chronic. |
|
| Chronic infection | 4 phases: | |
| HBeAg+, normal ALT, High DNA HBeAg+, fluctuating ALT, fluctuating DNA HBeAg-, normal ALT, low DNA HBeAg-, fluctuating ALT, fluctuating DNA |
||
| Outcome of chronic infection | 15% cirrhosis of which 20% decompensate and 5% get HCC. | Cirrhosis is slowly progressive 15% get cirrhosis at 20 years of which 5% decompensate per year, 1% get HCC per year and 4% die per year. |
| HDV relationship | Coinfection -> usually self limited; but⬆ risk of acute liver failure (compared to superinfection). No increased risk of chronic infection. |
None |
| Superinfection: ALL develop chronic HBV can present as acute severe hepatitis. |
None | |
| Chronic HDV -> rapid progression to cirrhosis. | None | |
| HCC association | Accounts for 50% of HCC; mostly after onset of cirrhosis. | accounts for 20% of HCC; but HCC only occurs after cirrhosis has developed. |
| ⬆viral load increases risk | ||
| Immune complexe mediated extrahepatic phenomena are less common in Hep C than in Hep B, except for essential mixed cryoglobulinaemia | ||
| Extrahepatic manifestations | "Serious Pirates Plundered Nine gold diamond chests" | Arthritis, myalgia, Sjogrens, kerato. conj. sicca, Mooren corneal ulcer, porphyria cutanea tarda, lichen planus, asymptomatic mixed cryoglobulinaemia (Type II cgb), membranoproliferative glomerulonephritis |
| Initially cryoglobulinaemia was described in hepaitits B. Also causes a "mixed cryoglublinaemia". | Essential mixed Cryoglobulinaemia is commoner in Hep C: Mnemonic: C-C. "mixed" means Rheumatoid factor, IgG, Hep C virus RNA and complement. |
|
| Treatment | 90% clearance rate with treatment! |
| Painful | Painless |
|---|---|
| Corneal abrasion | Lens dislocation |
| Keratitis | Vitreous haemorrhage |
| Acute Glaucoma | Acute maculopathy |
| Hyphema | Retinal detachment |
| Endophthalmitis | Retinal artery occlusion |
| Anterior Uveitis | Retinal Vein occlusion |
| Optic Neuritis | Ischemic optic neuropathy |
Symptoms
| Acute | Subacute | Chronic |
|---|---|---|
| Occurs in previously sensitized individuals | ||
| Fever, chills (unlike asthma), cough, chest tightness | exertional dyspnea, productive cough, fatigue, and weight loss, no fever. | |
| 4 - 8 hours after exposure | Months to years | |
| Occurs with high level antigen exposure | Occurs with low level antigen exposure (like a bird owner) | |
| Physical: fine crackes, NO WHEEZING | Can be complicated with cor pulmonale / respiratory failure. | |
| Airway obstruction is unusual | Can cause a restrictive pattern |
Investigations
CXR - Non specific.
HRCT - profuse, poorly defined centrilobular micronodules is the most characteristic findings. Fibrosis in Chronic HP.
BAL - Lymphocytosis with CD8+ predominance. (lymphocytosis with CD4+ predominant is seen in sarcoidosis)
Treatment: